Development of T cell receptor repertoires during childhood in health and disease

By Emma A., Bunia A., Othilia FS., Tobias C. & Joanna R.

Group 21

Introduction

Based on the article Mitchell et al. (2022)
Allele repertoire development during childhood and type 1 diabetes
Two groups of patients, case and control
Returns four times for observations

Materials:

1. Data from immunoSEQ ANALYZER

Methods:

1. Base R
1. Tidyverse R
2. PCA analysis
3. MCA analysis

Data Description

Original data (01_dat_load.tsv)

[1] 359  12
# A tibble: 359 × 2
   sample_name sample_tags                                                      
   <chr>       <chr>                                                            
 1 310183_TCRB 06 Years, 6 Years at visit, Caucasian, Control, Control 022, GAD…
 2 310110_TCRB 0 Years at visit, 09 Months, 6.37808219178082 Years at diagnosis…
 3 310206_TCRB 0 Years at visit, 10 Months, 10.558904109589 Years at diagnosis,…
 4 310288_TCRB 09 Years, 9 Years at visit, 9.56986301369863 Years at diagnosis,…
 5 310271_TCRB 02 Years, 2 Years at visit, 6.87397260273973 Years at diagnosis,…
 6 310244_TCRB 05 Years, 18.0438356164384 Years at diagnosis, 5 Years at visit,…
 7 310137_TCRB 07 Years, 7 Years at visit, Caucasian, Control, Control 014, Fem…
 8 310258_TCRB 12 Years, 12 Years at visit, 12.958904109589 Years at diagnosis,…
 9 310127_TCRB 04 Years, 11.6821917808219 Years at diagnosis, 4 Years at visit,…
10 310300_TCRB 17 Years, 17 Years at visit, 17.7561643835616 Years at diagnosis…
# ℹ 349 more rows
[1] 10

Data Wrangling

Augmented data (03_dat_aug.tsv)

[1] 13824    24
# A tibble: 10 × 8
   sample_name case_control    id age_diagnosis antibody expression allele  
   <chr>       <chr>        <dbl>         <dbl> <chr>         <dbl> <chr>   
 1 310102_TCRB Case             1          13.0 GAD65             0 HLA_A   
 2 310102_TCRB Case             1          13.0 GAD65             0 HLA_A   
 3 310102_TCRB Case             1          13.0 GAD65             0 HLA_B   
 4 310102_TCRB Case             1          13.0 GAD65             0 HLA_B   
 5 310102_TCRB Case             1          13.0 GAD65             0 HLA_C   
 6 310102_TCRB Case             1          13.0 GAD65             0 HLA_C   
 7 310102_TCRB Case             1          13.0 GAD65             0 HLA_DPA1
 8 310102_TCRB Case             1          13.0 GAD65             0 HLA_DPA1
 9 310102_TCRB Case             1          13.0 GAD65             0 HLA_DPB1
10 310102_TCRB Case             1          13.0 GAD65             0 HLA_DPB1
# ℹ 1 more variable: subtype <chr>

Antibody Expression

Antibody Expression, PCA

<<<<<<< HEAD

=======

>>>>>>> c0ba492e91ff780860805582a7f325f66fdfbe82

HLA Expression

<<<<<<< HEAD

HLA Expression, PCA

=======

HLA Expression, MCA

>>>>>>> c0ba492e91ff780860805582a7f325f66fdfbe82

Discussion

  • Patterns between antibody expressions. Suggests need for PCA.
  • Two components explain majority of variance in data.
  • Two clusters form between variables.
  • Dominant allele subtypes in case subjects.
  • Insufficient 2D variance explanation.

Limitations

  • Missing values for control subjects
  • Relatively small data set

Conclusion

  • Clear differences exist between case and control subjects, both in terms of antibody expression and in terms of allele subtypes.
  • Suggests that both antibody expression and allele subtype are involved in the development of diabetes in children.
  • Based on our results, HLA-DQB1*0202, HLA-B*4402, HLA-A*2402, and HLA-B*0702 could have a direct influence on type 1 diabetes.
<<<<<<< HEAD

THANK YOU for listening

=======

THANK YOU for listening

>>>>>>> c0ba492e91ff780860805582a7f325f66fdfbe82